[摘要] 目的
探討胃轉(zhuǎn)移性乳腺浸潤性小葉癌(ILC)的臨床病理特征及診斷要點。
方法 分析1例胃轉(zhuǎn)移性ILC病人的臨床病理特征、免疫表型及臨床表現(xiàn),并復(fù)習(xí)相關(guān)文獻。
結(jié)果 本文病人既往有胃低分化腺癌病史,1年后發(fā)現(xiàn)左乳包塊,經(jīng)穿刺活檢診斷為ILC。結(jié)合病史、胃黏膜和乳房穿刺活檢以及免疫組織化學(xué)檢查結(jié)果,最終診斷為胃轉(zhuǎn)移性ILC。
結(jié)論 ILC胃轉(zhuǎn)移較為罕見。當(dāng)有ILC病史的病人出現(xiàn)胃低黏附性癌且不伴有原位癌時,應(yīng)考慮ILC胃轉(zhuǎn)移的可能性,并可通過胃鏡檢查、活檢及免疫組織化學(xué)染色加以鑒別。
[關(guān)鍵詞] 乳腺腫瘤;腫瘤轉(zhuǎn)移;胃腫瘤;診斷,鑒別;免疫組織化學(xué);病例報告
[中圖分類號] R737.9
[文獻標(biāo)志碼] B
[文章編號] 2096-5532(2024)05-0775-03
doi:10.11712/jms.2096-5532.2024.60.150
[網(wǎng)絡(luò)出版] https://link.cnki.net/urlid/37.1517.r.20241029.1757.004;2024-10-30 14:57:02
Invasive lobular carcinoma of the breast with gastric metastasis: a case report and literature review
CHEN Zhaoxu, WANG Xiao, ZHAO Peng, ZHAO Jing, FU Guangming, WANG Chengqin
(Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China)
[Abstract]Objective To investigate the clinicopathological features and key diagnostic points of invasive lobular carcinoma (ILC) of the breast with gastric metastasis.
Methods One ILC patient with gastric metastasis was analyzed in terms of clinicopathological features, immunophenotypes, and clinical manifestations, and related articles were reviewed.
Results A female patient, aged 45 years, who had a previous history of poorly differentiated gastric adenocarcinoma was found to have a mass in the left breast one year later and was diagnosed with ILC by aspirationbiopsy. Based on medical history, aspirationbiopsy of gastric mucosa and breast, and immunohistochemistry, the patient was finally diagnosed with ILC with gastric metastasis.
Conclusion ILC with gastric metastasis is relatively rare. The possibility of gastric metastasis of ILC should be considered when a patient with the history of ILC is found to have low-adhesion gastric carcinoma without carcinoma in situ, and gastroscopy, biopsy, and immunohistochemical staining can be used for differential diagnosis.
[Key words] breast neoplasms; neoplasm metastasis; stomach neoplasms; diagnosis, differential; immunohistochemistry; case reports
乳腺浸潤性小葉癌(ILC)是乳癌中第二常見的組織學(xué)類型,占所有乳癌的2%~18%[1-2]。其轉(zhuǎn)移方式與浸潤性導(dǎo)管癌不同,較少發(fā)生實質(zhì)性臟器(肺、肝和腦)的轉(zhuǎn)移,而更容易轉(zhuǎn)移至卵巢、腹膜、胃腸道及骨等處[3-4]。據(jù)文獻報道,ILC的胃轉(zhuǎn)移發(fā)生率高于浸潤性導(dǎo)管癌[5]。胃轉(zhuǎn)移性腫瘤常見的表現(xiàn)是整個胃壁增厚(似革囊胃),鏡下細(xì)胞彌散分布,黏附性差,不形成明確包塊,易誤診為原發(fā)性胃低分化腺癌。本文報告1例胃轉(zhuǎn)移性ILC病例并復(fù)習(xí)相關(guān)文獻,總結(jié)該病的臨床病理特征、免疫表型及臨床表現(xiàn),以提高對該病的認(rèn)識。
1 病例報告
病人,女,45歲。因“無明顯誘因頸部疼痛,腰部及雙下肢疼痛,行動受限1月”于2017年12月到我院就診。對病人行正電子發(fā)射斷層掃描/計算機斷層掃描(PET/CT)檢查有以下表現(xiàn):①胃壁彌漫性增厚,代謝輕度增高;②枕骨、雙側(cè)肱骨、鎖骨、胸骨、椎骨、股骨等全身多發(fā)骨質(zhì)破壞;③肝胃間隙、肝門區(qū)、脾胰尾間、腹膜后多發(fā)增大淋巴結(jié);④腹腔積液;⑤大網(wǎng)膜、腸系膜輕度增厚、模糊;⑥其余臟器未見異常。臨床診斷為胃癌合并上述部位多發(fā)轉(zhuǎn)移的可能性較大。遂行胃鏡活檢,病理診斷為胃低分化腺癌,臨床按照胃癌伴全身多處轉(zhuǎn)移進行相應(yīng)治療。1年后(2018年12月)病人無意中在左乳房發(fā)現(xiàn)了1個核桃大小的包塊。超聲檢查示:左乳頭內(nèi)上方局部腺體增厚,回聲紊亂,范圍約3.2 cm×1.7 cm,形態(tài)不規(guī)則,邊界不清,建議行乳房包塊穿刺活檢。
胃鏡活檢病理結(jié)果顯示,低倍鏡(40倍)下見腫瘤細(xì)胞彌漫性分布,細(xì)胞體積小且較一致(圖1A);中倍鏡(100倍)下見腫瘤細(xì)胞彌散增殖,失去黏附,部分細(xì)胞呈串行樣排列,視野下方可見少量胃腺體,未見明確的低級別/高級別上皮內(nèi)瘤變,病理診斷為胃低分化腺癌(圖1B),但未行免疫組化檢測。1年后行左乳包塊穿刺活檢,高倍鏡(200倍)下可見
條索狀或單行線狀排列的細(xì)胞,細(xì)胞體積小,形態(tài)較一致,胞漿粉染,核偏位(圖1C)。免疫組化檢測顯示:細(xì)胞角蛋白7(CK7)、雌激素受體(ER)、孕激素受體(PR)、GATA結(jié)合蛋白3(GATA3)、乳腺球蛋白(Mammaglobin)均陽性,P120胞漿陽性,上皮細(xì)胞鈣黏蛋白(E-Cadherin)、細(xì)胞角蛋白20(CK20)、絨毛蛋白(Villin)、人表皮生長因子受體2(HER2)均陰性,Ki-67增殖指數(shù)為20%。結(jié)合免疫組化染色結(jié)果,診斷為ILC。查閱病人病史并復(fù)習(xí)既往胃鏡活檢蘇木精-伊紅(HE)染色切片,發(fā)現(xiàn)乳腺腫瘤鏡下形態(tài)與1年前胃部腫瘤相似。因此,對胃鏡活檢組織補充了免疫組化檢查,結(jié)果顯示,CK7(圖1D)、GATA3(圖1F)和ER(圖1G)均陽性,而CK20(圖1E)和E-Cadherin(圖1H)均陰性。根據(jù)胃鏡活檢結(jié)果,結(jié)合病史及免疫組化結(jié)果,最終診斷為ILC胃轉(zhuǎn)移。
2 討" 論
ILC的胃部轉(zhuǎn)移相對罕見[1,6]。據(jù)文獻報道,乳癌從就診到轉(zhuǎn)移的平均時間為6~7年[7]。因此,本文病人先出現(xiàn)胃轉(zhuǎn)移灶,而直到1年后才發(fā)現(xiàn)乳房原發(fā)灶是極其罕見的。既往有文獻報道,遠(yuǎn)處轉(zhuǎn)移部位(宮頸、胃)先于ILC的發(fā)生,其中1例以宮頸轉(zhuǎn)移為首發(fā)病灶,2年半后才發(fā)現(xiàn)原發(fā)乳房包塊[8]。乳癌的胃轉(zhuǎn)移發(fā)生率較低,而以胃腫瘤為首發(fā)癥狀的轉(zhuǎn)移性ILC更為罕見[9]。ILC轉(zhuǎn)移非常隱匿,可間隔1年甚至更長時間,有文獻報道稱可達10年之久[10]。
胃轉(zhuǎn)移性ILC的臨床表現(xiàn)、影像學(xué)檢查和胃鏡檢查結(jié)果無特異性,與原發(fā)性胃癌表現(xiàn)相似,鑒別診斷困難[11-12],診斷轉(zhuǎn)移性乳癌需要敏感和特異的乳腺標(biāo)記物。聯(lián)合檢測CK7和CK20有助于確定腺癌的原發(fā)部位[13]。本文病人胃鏡活檢免疫組織化學(xué)染色示,CK7陽性表達,CK20陰性表達,提示胃低分化癌為非原發(fā)性[14]。同時,ER陽性表達提示乳癌來源可能性大。既往研究結(jié)果顯示,轉(zhuǎn)錄因子GATA3在正常乳腺腺腔細(xì)胞中表達,診斷乳腺原發(fā)腫瘤的靈敏度為100%,特異度為98%[11]。GATA3在該病人中的陽性表達進一步提示胃部腫瘤為乳癌轉(zhuǎn)移所致。此外,E-Cadherin陰性表達提示了其病理類型為ILC。上述免疫組織化學(xué)染色結(jié)果充分提示,該病人的胃部腫瘤為乳癌轉(zhuǎn)移性病變,而非原發(fā)性腫瘤,可明確診斷為胃轉(zhuǎn)移性ILC。
關(guān)于ILC胃轉(zhuǎn)移的可能機制有以下幾種推測。①胃黏膜中幽門螺桿菌和炎癥介質(zhì)可以為吸引腫瘤細(xì)胞進入胃部創(chuàng)造有利的環(huán)境。②原發(fā)腫瘤與轉(zhuǎn)移瘤的時間間隔較長可能是腫瘤細(xì)胞的一種轉(zhuǎn)移性休眠現(xiàn)象,增殖活性低的腫瘤細(xì)胞在播種過程中不產(chǎn)生繼發(fā)性腫瘤,但仍能存活。經(jīng)過一段時間后,通過基因變化和與微介質(zhì)的相互作用獲得侵襲能力,從而形成轉(zhuǎn)移瘤[10]。因此,對于ILC病人,臨床應(yīng)注意全面系統(tǒng)的檢查,定期進行胃鏡檢查,以重視胃腸道轉(zhuǎn)移的可能性。當(dāng)光鏡下顯示胃黏膜固有腺體保存完好且無明確上皮內(nèi)瘤變時,應(yīng)注意轉(zhuǎn)移瘤的可能性。此外,有研究顯示,E-Cadherin(CDH1)基因的種系突變與遺傳性彌漫性胃癌和ILC密切相關(guān)[15-18]。CDH1基因突變增加患胃癌風(fēng)險的同時,其攜帶也增加了患ILC的風(fēng)險,進而導(dǎo)致乳癌-胃癌綜合征[19]。因此,有必要研究兩者之間的關(guān)系,通過CDH1基因的相關(guān)檢測來排除這種雙發(fā)癌的可能性。在治療方案上,胃轉(zhuǎn)移性ILC主要選擇化療、內(nèi)分泌治療或聯(lián)合治療,緩解率為32%~53%,生存時間可延長2~3年[7,20]。
綜上所述,本病例和以往的文獻報道表明,ILC的轉(zhuǎn)移模式是非常獨特的。當(dāng)女性病人乳房之外其他部位出現(xiàn)低黏附性癌且不伴有原位癌時,應(yīng)考慮轉(zhuǎn)移性ILC的可能性,并可以通過胃鏡檢查、活檢及免疫組化染色等方法進行鑒別[21],以獲得準(zhǔn)確的病理診斷,并給予病人適當(dāng)?shù)闹委?。我們將密切關(guān)注該病人病情的變化,必要時加做基因檢測可能有助于揭示本病例的基因背景及潛在發(fā)病機制。同時,以胃轉(zhuǎn)移為首發(fā)表現(xiàn)的轉(zhuǎn)移性ILC研究較少,有必要積累大量資料進一步研究,從而為胃轉(zhuǎn)移性ILC病人提供科學(xué)的診斷和治療方案。
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(本文編輯 牛兆山)
[收稿日期]2023-08-28; [修訂日期]2023-10-23
[基金項目]山東省自然科學(xué)基金面上項目(ZR2022MH206)
[第一作者]陳召旭(1996-),女,碩士研究生。
[通信作者]王成勤(1977-),女,博士,副教授,碩士生導(dǎo)師。E-mail:wcq0879@126.com。